Masaki Imai1, Tokiko Watanabe2, Maki Kiso2, Noriko Nakajima3, Seiya Yamayoshi2, Kiyoko Iwatsuki-Horimoto2, Masato Hatta4, Shinya Yamada2, Mutsumi Ito2, Yuko Sakai-Tagawa2, Masayuki Shirakura5, Emi Takashita5, Seiichiro Fujisaki5, Ryan McBride6, Andrew J Thompson6, Kenta Takahashi3, Tadashi Maemura2, Hiromichi Mitake2, Shiho Chiba4, Gongxun Zhong4, Shufang Fan4, Kohei Oishi2, Atsuhiro Yasuhara2, Kosuke Takada2, Tomomi Nakao2, Satoshi Fukuyama2, Makoto Yamashita2, Tiago J S Lopes7, Gabriele Neumann4, Takato Odagiri5, Shinji Watanabe5, Yuelong Shu8, James C Paulson6, Hideki Hasegawa3, Yoshihiro Kawaoka9. 1. Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan. Electronic address: mimai@ims.u-tokyo.ac.jp. 2. Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan. 3. Department of Pathology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan. 4. Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Sciences, University of Wisconsin-Madison, Madison, WI 53711, USA. 5. Influenza Virus Research Center, National Institute of Infectious Diseases, Musashimurayama, Tokyo 208-0011, Japan. 6. Departments of Molecular Medicine & Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA. 7. Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan; Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Sciences, University of Wisconsin-Madison, Madison, WI 53711, USA. 8. National Institute for Viral Disease Control and Prevention, China Centers for Disease Control and Prevention, Beijing 102206, China. 9. Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan; Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Sciences, University of Wisconsin-Madison, Madison, WI 53711, USA; Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan. Electronic address: yoshihiro.kawaoka@wisc.edu.
Abstract
Low pathogenic H7N9 influenza viruses have recently evolved to become highly pathogenic, raising concerns of a pandemic, particularly if these viruses acquire efficient human-to-human transmissibility. We compared a low pathogenic H7N9 virus with a highly pathogenic isolate, and two of its variants that represent neuraminidase inhibitor-sensitive and -resistant subpopulations detected within the isolate. The highly pathogenic H7N9 viruses replicated efficiently in mice, ferrets, and/or nonhuman primates, and were more pathogenic in mice and ferrets than the low pathogenic H7N9 virus, with the exception of the neuraminidase inhibitor-resistant virus, which showed mild-to-moderate attenuation. All viruses transmitted among ferrets via respiratory droplets, and the neuraminidase-sensitive variant killed several of the infected and exposed animals. Neuraminidase inhibitors showed limited effectiveness against these viruses in vivo, but the viruses were susceptible to a polymerase inhibitor. These results suggest that the highly pathogenic H7N9 virus has pandemic potential and should be closely monitored.
Low pathogenic H7N9pan class="Species">influenza viruses have recently evolved to become highly pathogenic, raising concerns of a pandemic, particularly if these viruses acquire efficient human-to-human transmissibility. We compared a low pathogenic H7N9 virus with a highly pathogenic isolate, and two of its variants that represent neuraminidase inhibitor-sensitive and -resistant subpopulations detected within the isolate. The highly pathogenic H7N9 viruses replicated efficiently in mice, ferrets, and/or nonhuman primates, and were more pathogenic in mice and ferrets than the low pathogenic H7N9 virus, with the exception of the neuraminidase inhibitor-resistant virus, which showed mild-to-moderate attenuation. All viruses transmitted among ferrets via respiratory droplets, and the neuraminidase-sensitive variant killed several of the infected and exposed animals. Neuraminidase inhibitors showed limited effectiveness against these viruses in vivo, but the viruses were susceptible to a polymerase inhibitor. These results suggest that the highly pathogenic H7N9 virus has pandemic potential and should be closely monitored.
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